Evaluation of vancomycin and gentamicin dialysis clearance using in vivo and in vitro systems

Advances in hemodialysis (HD) techniques have increased the potential for drug removal. Quantifying drug clearance in clinical studies for all possible dialysis conditions is impractical, given the variability in dialysis conditions. The purpose of this study was to determine the dialysis clearance (CL(D)) of vancomycin and gentamicin using in vitro and in vivo methods and evaluate the applicability of in vitro data. In vitro dialysis was used to determine the CL(D) of vancomycin and gentamicin under conditions of intermittent HD (IHD) and sustained low-efficiency dialysis (SLED). Two Fresenius polysulfone dialyzers were studied: F180NR for IHD and F50 for SLED. Data were compared with in vivo CL(D) determined in patients with end-stage renal disease receiving IHD and from the literature for SLED. Under IHD conditions, in vitro CL(D) of vancomycin and gentamicin was 131 ± 3 and 154 ± 3 mL/min, respectively, and under SLED condition it was 72 ± 9 and 84 ± 11 mL/min, respectively. These values were 11-27% higher than in vivo CL(D) for IHD (103 ± 15 mL/min for vancomycin and 132 ± 25 mL/min for gentamicin) and SLED (63 mL/min for vancomycin and 76 ± 38 mL/min for gentamicin). There was a statistically significant difference in vancomycin clearance by IHD for the in vitro study compared with in vivo data (p = 0.012), but not for gentamicin (p = 0.18). In vitro methods overestimated in vivo CL(D), but are reasonable to assist with drug regimen design if one considers the limitations.